Secretory organelles in ECL cells: effects of pharmacological blockade of the gastrin/CCK2 receptor versus its elimination by gene targeting

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Histamine-producing ECL cells are numerous in the stomach. They express gastrin/CCK2 receptors and respond to gastrin by releasing histamine. Ultrastructurally, they display numerous and very characteristic secretory organelles: granules, secretory vesicles and microvesicles. This paper focuses on the impact of the gastrin/CCK2 receptor on the ultrastructure of the ECL cells. The effects of pharmacological blockade of the receptor are compared with the effects of receptor elimination following selective gene targeting. Long-term administration of powerful gastrin/CCK2 receptor antagonists was found to induce hypotrophy of rat stomach ECL cells with reduced number of granules, secretory vesicles and microvesicles. In gastrin/CCK2 receptor knockout mice ECL cells, i.e., histamine-storing cells with the characteristic ultrastructure of ECL cells, had disappeared from the oxyntic mucosa and been replaced by a novel population of endocrine-like cells. These cells harbored granules and microvesicles, but were devoid of histamine and secretory vesicles. We suggest that the gastrin/CCK2 receptor is important for the proper differentiation of the ECL cells and for maintaining their characteristic ultrastructure.

Affiliations:
1: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, University Hospital in Trondheim, Olav Kyrres gate 17, N-7006 Trondheim, Norway;
2: Department of Pharmacology, University of Lund, Lund, Sweden;
3: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

10.1163/156856005774423818

/content/journals/10.1163/156856005774423818

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Secretory organelles in ECL cells: effects of pharmacological blockade of the gastrin/CCK2 receptor versus its elimination by gene targeting